title: Synthesis and α-glucosidase inhibitory activity evaluation of N-substituted aminomethyl-β-d-glucopyranosides.
abstract: A series of N-substituted 1-aminomethyl-β-d-glucopyranoside derivatives was prepared. These novel synthetic compounds were assessed in vitro for inhibitory activity against yeast α-glucosidase and both rat intestinal α-glucosidases maltase and sucrase. Most of the compounds displayed α-glucosidase inhibitory activity, with IC50 values covering the wide range from 2.3μM to 2.0mM. Compounds 19a (IC50=2.3μM) and 19b (IC50=5.6μM) were identified as the most potent inhibitors for yeast α-glucosidase, while compounds 16 (IC50=7.7 and 15.6μM) and 19e (IC50=5.1 and 10.4μM) were the strongest inhibitors of rat intestinal maltase and sucrase. Analysis of the kinetics of enzyme inhibition indicated that 19e inhibited maltase and sucrase in a competitive manner. The results suggest that the aminomethyl-β-d-glucopyranoside moiety can mimic the substrates of α-glucosidase in the enzyme catalytic site, leading to competitive enzyme inhibition. Moreover, the nature of the N-substituent has considerable influence on inhibitory potency.
authors.affiliation: College of Pharmacy, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Bian
authors.forename: Xiangni
authors.initials: X
authors.lastname: Fan
authors.forename: Changhu
authors.initials: C
authors.lastname: Ke
authors.forename: Yajun
authors.initials: Y
authors.lastname: Luan
authors.forename: Guilan
authors.initials: G
authors.lastname: Zhao
authors.forename: Aiguo
authors.initials: A
authors.lastname: Zeng
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D007422:Intestines / Q000201:enzymology; D007700:Kinetics; D011485:Protein Binding; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005960:Glucosides; D065089:Glycoside Hydrolase Inhibitors; D000520:alpha-Glucosidases
keywords: 1-Aminomethyl-β-d-glucopyranoside; Sugar mimic; Synthesis; α-Glucosidase